Neonatal lung disease among toughest challenges

Therapies to help premature babies breathe can cause permanent damage

Nothing announces the arrival of a new child more loudly than his or her first squeal of outrage, the product of an unexpected slap on the bottom and a healthy pair of brand new lungs.

It’s a sound rarely heard from babies born prematurely, who often enter the world with lungs neither fully formed nor functional. Indeed, premature newborns are at greater risk of suffering neonatal lung disease, a collection of ailments ranging from pulmonary hypoplasia (incomplete lung development) to infant respiratory distress syndrome, a condition caused by insufficient production of lung surface proteins vital to lung function.

Treating neonatal lung disease is among medicine’s toughest challenges. Premature babies or “preterms” typically weigh just a few pounds. Their grip on life may be tentative and precarious. Therapies to help them breathe — and survive — can cause permanent damage.

We asked Dr. Lawrence S. Prince, chief of neonatology at UC San Diego Health System and at Rady Children’s Hospital-San Diego, to talk about the causes of neonatal lung disease and research efforts to help preterms grow their own lungs.

Q: Are neonatal lung diseases primarily the consequence of underdevelopment and premature birth or do other factors, such as genetics, play a significant role?

A: Neonatal lung disease is clearly the result of being born premature or preterm. In some preterm infants, the lungs fail to develop, while other body parts grow normally. Most likely, this arrested lung development results from the unanticipated early exposure of the lung to air and bacteria in the outside world. Activation of the lung immune system then somehow destroys the normal blueprint for forming a mature lung. However, not all infants develop persistent lung disease, suggesting there may be a genetic component that we do not yet understand. Lung disease in preterm infants is therefore a classic mix of “nature versus nurture,” with both genetic risk and environmental exposures determining which patients get the disease.

Q: Are there fundamental differences in how the lungs of a premature newborn develop compared with a baby who is full-term?

A: The tiny spaces in the lung that actually allow oxygen to get into our bloodstream and carbon dioxide to leave our body are called alveoli. These structures don’t form until the last month or two of pregnancy. Infants who are born preterm do not yet have any alveoli, and subsequent lung development occurs much more slowly than babies who remain inside their mothers. Because of their immature lung structures, preterm infants sometime need extra oxygen or a mechanical ventilator to breathe even when they reach the size and maturity of a full-term infant. In the most critically ill preterm infants, lung development stops completely and alveoli never form.

Q: What are the specific risks and challenges in promoting and maintaining the respiratory health of newborns with neonatal lung diseases?

A: The biggest challenge in neonatal lung disease is balancing the amount of intensive care we provide with minimizing the amount of potential injury done to vulnerable, immature lungs. Preterm infants often need mechanical ventilation and extra oxygen to survive, but we know that this support can produce long-term damage and increase the chance of lung infection or pneumonia. We therefore closely monitor exactly what each preterm infant receives every minute of the day and night, quickly adjusting our treatment to remove ventilators and reduce oxygen exposure as soon as possible. This takes many specially trained personnel working around the clock for each patient. Our next biggest concern is how to prevent infection. If preterm infants get bacterial or viral pneumonia, even after they go home, they are more likely to end up with long-term lung disease.

Q: Much of your research involves lung regeneration and growth. What kind of reparative power do lungs have?

A: My laboratory has been approaching this problem from several directions. We spend a lot of time trying to figure out which cells and molecules in the lung are damaged by oxygen and infection. In addition, we are using various growth factor and stem cell approaches to see what can make the damaged lung grow normally. Our hope is to both prevent oxygen and infection from causing long-term lung damage and to stimulate normal lung growth and development in those preterm infants that have suffered lung injury.